Process for producing bone cement containing active substances

Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Processes of preparing a desired or intentional composition...

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Details

523118, 524533, 424423, A61K 6087, A61F 228, C08L 3312

Patent

active

061600334

DESCRIPTION:

BRIEF SUMMARY
The invention relates to a process for the preparation of bone cements comprising active compound and to bone replacement materials or implantable drug depots which can be produced therefrom.
Bone cements, bone replacement materials and implantable drug depots based on acrylate polymers have been known for a long time. Polymer materials based on acrylic and/or methacrylic esters have proved themselves here on the basis of their biocompatibility, their excellent strength properties, their favourable properties in respect of the release of incorporated pharmaceutical active compounds and, last but not least, on the basis of their utility-oriented processability.
Customary bone cements are composed of from about 50 to 75% by weight of a solid component which consists of a finely divided polymer of acrylic and/or methacrylic esters and, if desired, of further additives such as polymerization catalysts, X-ray contrast media, fillers and colorants, and of from about 25 to 50% by weight of a liquid component which consists of an acrylic and/or methacrylic ester monomer and, if desired, further additives such as polymerization accelerators and stabilizers. For use, the solid and the liquid component are combined to form a liquid to semisolid paste, which is optionally brought into a desired shape or is applied at the implantation site of a prosthesis to cement it in. The composition cures by means of the polymerization reaction that is induced with the mixing of the components.
A very common bone cement, for example, is one which, in a standard pack, comprises two bags of about 40 g of polymer powder each and two ampoules of 20 ml of monomer liquid each. The powder is a fine bead polymer of methyl methacrylate with a copolymer content of methyl acrylate. About 0.5% of dibenzoyl peroxide is added to the powder as a catalyst. During preparation the material is identified by copolymerizing small amounts of chlorophyll. The powder additionally comprises a customary X-ray contrast medium such as, for example, zirconium dioxide. The associated liquid consists of monomeric methyl methacrylate, to which about 0.7% of dimethyl-p-toluidine is added as a polymerization accelerator and small amounts of hydroquinone are added as a stabilizer. This liquid is also, in general, coloured with a small amount of chlorophyll for identification. The powder, packaged in polyethylene bags, is sterilized with ethylene oxide. The liquid is subjected to sterile filtration and dispensed into glass ampoules.
When 2 parts by weight of powder are mixed together with one part by weight of liquid, the dibenzoyl peroxide reacts with the dimethyl-p-toluidine in the liquid, which prompts the free-radical polymerization. The mixture is formulated such that it can be used as a doughy paste after only about one minute. This paste remains kneadable for a number of minutes and then begins to cure, giving off heat as it does so. After about 5 to 10 minutes the polymerization is essentially at an end. During the polymerization phase, for as long as the paste is still deformable, it can be brought into any desired shape, i.e. it can, for example, be introduced directly into the body for filling bone cavities or for cementing prostheses or can be used to produce shaped articles which cure outside the body and can then be used at any desired points of the body.
For numerous indications it is desirable for the bone cement to comprise pharmaceutical active compounds. Thus, bone cements comprising cytostatics can be employed for remedying bone defects following the removal of bone tumours. Bone cements which comprise antibiotics, antiseptics and, if desired, substances which promote bone growth are advantageous for cementing prostheses and for osteosynthesis. Shaped articles of bone cements comprising active compound can be implanted into soft tissue as local depots of active compound with delayed release of the active compound. Customary commercial bone cements with added antibiotics (e.g. Septopal.RTM.) are occasionally also used as active-compound vehicles f

REFERENCES:
patent: 4588583 (1986-05-01), Pietsch et al.
patent: 4722948 (1988-02-01), Sanderson
patent: 5650108 (1997-07-01), Nies
Buchholz et al, "Antibiotic loaded Acrylic Cement: Current Concepts," Clin. Orthopaedics and. Rel. Res., No. 190, pp. 96-108, Nov. 1984.

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